Carmustine Accord

Package Leaflet: Information for the User

Carmustine Accord, 100 mg, powder and solvent for concentrate for solution for infusion

for infusion
Carmustine

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

• 1. What Carmustine Accord is and what it is used for
• 2. What you need to know before you use Carmustine Accord
• 3. How to use Carmustine Accord
• 4. Possible side effects
• 5. How to store Carmustine Accord
• 6. Contents of the pack and other information

1. What Carmustine Accord is and what it is used for

Carmustine Accord is a medicine that contains the active substance carmustine. Carmustine belongs to a group of medicines called nitrosourea cytotoxics, which work by slowing down the growth of cancer cells.
Carmustine is used to treat adults with certain types of cancer, including:

• Brain tumors (glioblastoma, brainstem glioma, medulloblastoma, glioma, and ependymoma) and metastases to the brain
• Second-line therapy for non-Hodgkin's lymphoma and Hodgkin's disease
• Gastrointestinal tumors
• Malignant melanoma (skin cancer)
• As conditioning treatment before autologous hematopoietic stem cell transplantation in malignant hematological diseases (Hodgkin's disease/non-Hodgkin's lymphoma)

2. What you need to know before you use Carmustine Accord

When not to use Carmustine Accord:

• If you are allergic to carmustine or any of the other ingredients of this medicine (listed in section 6)
• If you have bone marrow suppression, which can cause a low platelet count, low white blood cell count, or low red blood cell count, due to chemotherapy or other causes
• If you have severe kidney problems
• In children and adolescents under 18 years of age
• In breastfeeding women

Warnings and precautions

Before starting treatment with Carmustine Accord, you should discuss this with your doctor, pharmacist, or nurse.
The main side effect of this medicine is delayed bone marrow suppression, which can cause fatigue, bleeding, and infections. Therefore, your doctor will monitor your blood counts every week for at least 6 weeks after each dose. Courses of treatment with Carmustine Accord should not be given more frequently than every 6 weeks. Before each dose, your doctor will check your blood counts.
Before starting treatment, liver, lung, and kidney function tests will be performed, which will be repeated regularly during treatment.
Since Carmustine Accord can cause lung damage, a chest X-ray and lung function tests will be performed before starting treatment (see also section "Possible side effects").
High-dose treatment with Carmustine Accord (up to 600 mg/m2) is only used in combination with subsequent autologous hematopoietic stem cell transplantation. High doses may increase the risk of toxic effects on the lungs, kidneys, liver, heart, and gastrointestinal tract, as well as infections and electrolyte disturbances (low potassium, magnesium, and phosphorus levels in the blood).
Abdominal pain (neutropenic enterocolitis) may occur as a side effect related to chemotherapy.

Children and adolescents

Carmustine Accord should not be used in children and adolescents under 18 years of age.

Carmustine Accord with other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription, such as:

• Phenytoin used for epilepsy
• Dexamethasone used as an anti-inflammatory and immunosuppressant
• Cimetidine used for stomach problems, such as indigestion
• Digoxin used for irregular heart rhythm
• Melphalan, an anticancer medicine

Using Carmustine Accord with alcohol

The amount of alcohol in this medicine may affect the way other medicines work.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy and fertility
Carmustine Accord should not be used during pregnancy, as it may harm the unborn baby. Therefore, it is not usually given to pregnant women. If used during pregnancy, the patient should be aware of the potential risks to the unborn baby. Women of childbearing potential should be advised to use effective contraception to prevent pregnancy during treatment with this medicine and for at least 6 months after treatment.
Men should use appropriate contraceptive measures during treatment with Carmustine Accord and for at least 6 months after treatment to prevent pregnancy in their partners.
Breastfeeding
You should not breastfeed while using this medicine and for 7 days after treatment. It is not known whether this medicine can harm newborns/infants.

Driving and using machines

Carmustine Accord has no or negligible influence on the ability to drive and use machines. However, you should consult your doctor before driving or operating any tools or machines, as the amount of alcohol in this medicine may impair your ability to drive or operate machines.

Carmustine Accord contains ethanol (alcohol)

This medicine contains 2.37 g of ethanol (alcohol) per vial, which is equivalent to 33.86 mg/kg. The amount of alcohol in the maximum dose (600 mg/m2) of this medicine is equivalent to 640 ml of beer or 256 ml of wine.
The amount of alcohol in this medicine may affect your ability to drive or operate machines. It may also affect your judgment and reaction time.
Patients with epilepsy or liver disease should consult their doctor or pharmacist before taking this medicine.
The amount of alcohol in this medicine may affect the way other medicines work. If you are taking other medicines, consult your doctor or pharmacist.
Pregnant or breastfeeding women should consult their doctor or pharmacist before taking this medicine.
Alcohol-dependent patients should consult their doctor or pharmacist before taking this medicine.
Since this medicine is usually administered slowly over 1-2 hours, the effect of alcohol may be reduced.

3. How to use Carmustine Accord

Carmustine Accord will always be given by a medical professional with experience in using anticancer medicines.

Adults

The dose depends on your health, body surface area, and response to treatment. The medicine is usually given no more frequently than every 6 weeks. The recommended dose of Carmustine Accord used as a single agent in previously untreated patients is 150-200 mg/m2 intravenously every 6 weeks.
The medicine can be given as a single dose or divided into daily infusions of 75-100 mg/m2 over 2 consecutive days. The dose is also dependent on whether Carmustine Accord is given with other anticancer medicines.
Doses will be increased according to the patient's response to treatment.
The recommended dose of Carmustine Accord given intravenously in combination with other chemotherapeutic agents before autologous hematopoietic stem cell transplantation is 300-600 mg/m2.

To avoid toxic effects on the bone marrow, blood counts will be frequently monitored, and the dose will be adjusted as necessary.

Method of administration

After reconstitution and dilution, Carmustine Accord is given intravenously in an infusion over 1-2 hours, protected from light. The infusion time should not be less than 1 hour, otherwise, burning and pain at the injection site may occur. The injection site will be monitored during the infusion.
The duration of treatment will be determined by your doctor and may vary from patient to patient.

Overdose

Since the medicine will be given by a doctor or nurse, it is unlikely that you will be given too much. If you have any concerns about the amount of medicine you have been given, tell your doctor or nurse.
If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Carmustine Accord can cause side effects, although not everybody gets them.

You should tell your doctor or nurse immediately if you notice any of the following:

any sudden wheezing, difficulty breathing, swelling of the eyelids, face, or lips, rash, or itching (especially if these affect your whole body), as well as a feeling of fainting. These may be signs of a severe allergic reaction.

Carmustine Accord may cause the following side effects:

Very common(may affect more than 1 in 10 people):

• Delayed bone marrow suppression (reduced production of blood cells), which can increase the risk of infections if the white blood cell count is low;
• Ataxia (lack of voluntary coordination of muscle movements);
• Dizziness;
• Headache;
• Transient eye redness, blurred vision due to retinal hemorrhage;
• Hypotension (low blood pressure);
• Phlebitis (inflammation of the veins) associated with pain, swelling, redness, and tenderness;
• Respiratory disorders (lung problems) associated with difficulty breathing. This medicine can cause severe (potentially life-threatening) lung damage. Lung damage can occur years after treatment. You should tell your doctor immediately if you experience any of the following symptoms: shortness of breath, persistent cough, chest pain, persistent weakness/fatigue.
• Severe nausea and vomiting;
• Skin inflammation if the medicine comes into contact with the skin;
• Accidental contact with the skin can cause temporary discoloration (darkening of the skin or nails)
• Common(may affect up to 1 in 10 people):
• Aplastic anemia and bone marrow dysplasias (abnormal development of the bone marrow). Possible symptoms include: gum bleeding, bone pain, fever, frequent infections, frequent nosebleeds or heavy bleeding, swollen lymph nodes in the neck, armpits, abdomen, or groin, pale skin, shortness of breath, weakness, fatigue, or general loss of energy;
• Anemia (low red blood cell count);
• Encephalopathy (brain disease). Possible symptoms include: muscle weakness in one area, inability to make decisions or poor concentration, involuntary muscle twitching, tremors, difficulty speaking or swallowing, seizures;
• Anorexia;
• Constipation;
• Diarrhea;
• Mouth and lip inflammation;
• Reversible liver toxicity with high-dose treatment. This condition can cause elevated liver enzymes and bilirubin levels (these are parameters measured in blood tests);
• Hair loss;
• Skin redness;
• Reactions at the injection site.

Rare(may affect up to 1 in 1,000 people):

• Veno-occlusive disease of the liver (progressive blockage of small veins in the liver) with symptoms such as fluid accumulation in the abdomen, enlarged spleen, severe bleeding from the esophagus, yellowing of the skin and whites of the eyes;
• Breathing problems due to interstitial fibrosis (with low-dose treatment);
• Kidney problems;
• Gynecomastia (breast enlargement in men).

Unknown(frequency cannot be estimated from the available data):

• Muscle pain;
• Seizures (including status epilepticus);
• Tissue damage due to leakage at the injection site;
• Infertility;
• Any signs of infection;
• It has been shown that carmustine has a harmful effect on the development of unborn babies.
• Electrolyte disturbances (including electrolyte imbalance, low potassium, magnesium, and phosphorus levels in the blood).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in the "Further information" section.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Carmustine Accord

The medicine will be stored by a medical professional or other authorized personnel.
The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month.
Store and transport at 2°C-8°C.
Store the vials in the outer carton to protect from light.
After reconstitution (reconstituted concentrate solution)

Chemical and physical stability of the reconstituted concentrate solution has been demonstrated for 24 hours at 2°C-8°C.
After dilution (diluted solution for infusion)

Chemical and physical stability of the diluted solution for infusion in 500 ml sodium chloride 9 mg/ml (0.9%) injection or 500 ml glucose 5% injection has been demonstrated for 4 hours at 20°C-25°C and protected from light. The solutions will also remain stable for 24 hours** in the refrigerator (2°C-8°C) and for a further 3 hours at 20°C-25°C, protected from light.
From a microbiological point of view, unless the method of opening, reconstitution, and dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.
The solution should be protected from light until administration is complete.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Carmustine Accord contains

The active substance is carmustine.
Each 30 ml vial of powder for concentrate for solution for infusion contains 100 mg of carmustine.
Each vial of solvent contains 3 ml of anhydrous ethanol.
After reconstitution with the supplied solvent and dilution in 27 ml of sterile water for injection, 1 ml of the solution contains 3.3 mg of carmustine.
Excipients:

• Powder: No excipients.
• Solvent: Ethanol, anhydrous.

What Carmustine Accord looks like and contents of the pack

Carmustine Accord is a powder and solvent for concentrate for solution for infusion.
Light yellow dry flakes or compacted dry mass in a 30 ml glass vial closed with a grey rubber stopper and an aluminum seal with a polypropylene cap.
The solvent is a clear, colorless solution in a 5 ml glass vial closed with a butyl rubber stopper and an aluminum seal with a polypropylene cap.
Pack sizes:

1 vial containing 100 mg of powder and 1 vial containing 3 ml of solvent.
10 vials containing 100 mg of powder and 10 vials containing 3 ml of solvent.
Not all pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warszawa
Tel: + 48 22 577 28 00

Manufacturer/Importer

Accord Healthcare Polska Sp.z o.o.
ul. Lutomierska 50
95-200 Pabianice
Laboratori Fundació Dau
C/ C, 12-14 Pol. Ind.
Zona Franca
08040 Barcelona
Spain
Accord Healthcare B.V.
Winthontlaan 200
3526KV Utrecht
Netherlands

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of last revision of the package leaflet: September 2024

Information intended for healthcare professionals only:
Below is a brief description of the preparation and/or administration, incompatibilities, dosing, overdose, or monitoring and laboratory tests, based on the current Summary of Product Characteristics.
Carmustine Accord powder for concentrate for solution for infusion does not contain preservatives and is not intended for use in multidose vials.
Reconstitution and further dilution should be carried out under aseptic conditions.
Provided the recommended storage conditions are maintained, the intact vial can be used up to the expiry date stated on the packaging.
Storage of carmustine at temperatures above 28°C may cause degradation of the substance, as carmustine has a low melting point (around 28°C to 29°C). A sign of degradation is an oily layer at the bottom of the vial visible in bright light. This product should not be used. In an intact vial, flakes with sharp edges or even a compacted mass may be visible, but without degradation of carmustine.
Reconstitution and dilution of the powder for concentrate for solution for infusion
Dissolve carmustine (100 mg powder) in 3 ml of the supplied sterile, chilled solvent (ethanol) in the primary packaging (brown glass vial). Carmustine should be completely dissolved in ethanol before adding sterile water for injection. Dissolution of the powder may take 3 minutes. Then, aseptically add 27 ml of sterile water for injection to the ethanol solution. The resulting 30 ml solution should be thoroughly mixed.
One milliliter of the solution contains 3.3 mg of carmustine in 10% ethanol, and its pH is 4 to 6.8.
The reconstituted solution is yellowish and practically free from visible particles.
The 30 ml solution should be further diluted immediately by adding 30 ml of the solution to 500 ml of sodium chloride 9 mg/ml (0.9%) injection or 500 ml glucose 5% injection.
Method of administration
Carmustine Accord is intended for intravenous administration after reconstitution and further dilution.
When reconstituting the powder using the supplied sterile solvent (3 ml vial), prepare the solution and then add a further 27 ml of sterile water for injection to obtain a yellowish solution. This solution should be further diluted in 500 ml of sodium chloride 9 mg/ml (0.9%) injection or glucose 5% injection.
The resulting infusion solution should be administered immediately in an intravenous infusion over 1-2 hours, protected from light. The infusion time should not be less than 1 hour, otherwise, burning and pain at the injection site may occur. The injection site should be monitored during the infusion.
Pregnant personnel should not handle this medicinal product.
Guidelines for the safe handling and disposal of cytotoxic medicines should be followed.
Dosing and laboratory tests
Initial doses
The recommended dose of Carmustine Accord used as a single agent in previously untreated patients is 150-200 mg/m2 intravenously every 6 weeks. The medicine can be given as a single dose or divided into daily infusions of 75-100 mg/m2 over 2 consecutive days.
When Carmustine Accord is used in combination with other medicines that have a myelosuppressive effect or in patients with reduced bone marrow reserve, the dose should be adjusted according to the patient's hematologic profile, as described below.
Monitoring and subsequent doses
A subsequent course of treatment with Carmustine Accord should only be given when the blood counts have returned to acceptable levels (platelet count above 100,000/mm3, white blood cell count above 4,000/mm3), which usually occurs within 6 weeks. Blood counts should be frequently monitored, and subsequent doses should not be given before 6 weeks due to the risk of delayed hematologic toxicity.
After the initial dose, subsequent doses should be adjusted according to the patient's hematologic response to the previous dose, both as a single agent and in combination with other myelosuppressive medicines. The following dose adjustment scheme is suggested:

In cases where the lowest level after the previous dose does not fall within the same row for white blood cells and platelets (e.g., white blood cell count >4,000 and platelet count <25,000), the value corresponding to the lowest percentage of the previous dose should be used (e.g., platelet count <25,000 - use a maximum of 50% of the previous dose).
There are no limitations on the duration of treatment with carmustine. If the tumor remains incurable or severe or intolerable side effects occur, treatment with carmustine should be discontinued.
Conditioning treatment before hematopoietic stem cell transplantation
Carmustine is given intravenously at a dose of 300-600 mg/m2 in combination with other chemotherapeutic agents to patients with malignant hematological diseases before hematopoietic stem cell transplantation.
Special populations
Children and adolescents
Carmustine should not be used in children and adolescents under 18 years of age due to safety concerns.
Elderly
Generally, in elderly patients, doses should be selected cautiously, and in particular, those with impaired liver, kidney, or heart function, as well as those taking other medicines, should be started on the lower end of the dose range due to the higher frequency of these conditions in this age group; careful monitoring of renal function and dose adjustment are recommended.